^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    GENE:

    MLH1 (MutL homolog 1)

    i
    Other names: MLH1, COCA2, FCC2, HNPCC, HNPCC2, MutL homolog 1
    1d
    A Web-Based Program (Kindred) to Improve the Understanding of Genetic Cancer Risk and Cancer Genetic Testing in African American Families (clinicaltrials.gov)
    P=N/A, N=150, Not yet recruiting, University of Michigan Rogel Cancer Center
    New trial
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    1d
    MLH1 promoter methylation-induced dMMR/MSS in endometrial cancer: case report. (PubMed, Discov Oncol)
    In conclusion, for endometrial cancer patients exhibiting dMMR by IHC but MSS by MSI testing, MLH1 promoter methylation testing becomes even more critical. This not only aids in screening for Lynch syndrome, enabling pathologists to make a more precise diagnosis, but also provides important guidance for clinical treatment decisions.
    Journal • IO biomarker • dMMR
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1)
    |
    MSI-H/dMMR
    5d
    Germline Variants in Bladder and Upper Tract Urothelial Cancers: Prevalence and Clinical Context in a Large Testing Registry. (PubMed, Eur Urol Open Sci)
    However, many patients with these variants have urothelial cancer of the bladder only. Broader genetic testing, particularly in those with a suggestive personal or family cancer history, may help identify patients at risk who might otherwise be missed.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    5d
    Genome Sequencing of Undiagnosed European Patients Suspected of Hereditary Cancer: Diagnostic Yield and Identification of Candidate Causative Variants. (PubMed, JCO Precis Oncol)
    Comprehensive resequencing of patients suspected of hereditary cancer increased the diagnostic yield by 6%. Detected pathogenic variants involved phenotype-related genes not previously analyzed or missed because of mosaicism. WGS further enables identification of novel gene associations and structural, deep intronic, or regulatory variants.
    Journal
    |
    TP53 (Tumor protein P53) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • BARD1 (BRCA1 Associated RING Domain 1) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit)
    8d
    Immunohistochemical Expression of MLH1 and MSH2 in Colorectal Carcinoma and Its Correlation With Clinicopathological Parameters. (PubMed, Cureus)
    MLH1 loss was closely linked to early-onset CRC and may point to a hereditary risk. Regular testing for MMR proteins can help with diagnosis, screening for Lynch syndrome, and choosing the best treatment.
    Journal • IO biomarker
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    8d
    Germline pathogenic variant spectrum and prevalence among colorectal cancer patients undergoing multigene panel testing in Kazakhstan. (PubMed, Sci Rep)
    Among overall identified PVs, six were novel: APC c.3405T > G, APC c.419_422delAGAG, PMS1 c.1258delC, MLH1 c.1291_1292delAT, NBN c.877delA, and EPCAM c.184 + 1G > A. The observed prevalence of clinically actionable PVs in both patients and their relatives highlights the potential clinical value of multigene panel testing and cascade screening strategies in Kazakhstan.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • PMS1 (PMS1 protein homolog 1)
    9d
    Hyperprogression after Anti-Programmed Death-1 Therapy in a Case of Sigmoid Colon Cancer with Lynch Syndrome. (PubMed, Surg Case Rep)
    This case underscores the importance of early response evaluation in ICI-treated MSI-H tumors. Rapid disease progression requires prompt differentiation between HPD and pseudoprogression, emphasizing the necessity of timely therapeutic modification.
    Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
    |
    KRAS mutation • MSI-H/dMMR • BRAF mutation • RAS wild-type • NRAS wild-type • KRAS G13 • NRAS G13
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
    9d
    NCI-2017-02296: Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes (clinicaltrials.gov)
    P2, N=60, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension • Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • POLE (DNA Polymerase Epsilon) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • BRD4 (Bromodomain Containing 4) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
    |
    PALB2 mutation • BRIP1 mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Lynparza (olaparib)
    9d
    A Pancreatic Cancer Screening Study in Hereditary High Risk Individuals (clinicaltrials.gov)
    P=N/A, N=200, Recruiting, Nuvance Health | Trial completion date: Nov 2026 --> Nov 2030 | Trial primary completion date: Nov 2026 --> Nov 2030
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation
    14d
    Prevalence and clinicopathologic features of mismatch repair-deficient endometrial cancer in Japanese patients younger than 50 years: a single-center prospective observational study. (PubMed, Int J Clin Oncol)
    In this prospective Japanese cohort, approximately one in four patients with EC had dMMR, with clinicopathologic features skewing toward a higher grade. Notably, many dMMR tumors were grade 2-3, suggesting that a substantial proportion of patients may fall outside the conventional criteria for fertility-sparing treatment.
    Observational data • Journal • Mismatch repair • dMMR
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    MSI-H/dMMR
    14d
    Characterizing therapeutic target antigen expression in anaplastic carcinoma of the ovary. (PubMed, Gynecol Oncol Rep)
    FOLR1 expression in the two cases was weak and below currently used clinical cutoffs for mirvetuximab soravtansine eligibility...Only a subset of anaplastic carcinomas of the ovary express targetable tumor antigens at low levels, suggesting that these may have limited benefit from antibody-drug conjugates. Likewise, due to mismatch repair proficiency and low tumor mutational burden, immunotherapy is unlikely to be effective in this rare disease.
    Journal • Tumor mutational burden • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • FOLR1 ( Folate receptor alpha ) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
    |
    HER-2 expression • TMB-L • FOLR1 expression
    |
    Elahere (mirvetuximab soravtansine-gynx)